IOSR Journal Of Pharmacy www.iosrphr.org

(e)-ISSN: 2250-3013, (p)-ISSN: 2319-4219

Volume 8, Issue 6 Version. I (June 2018), PP. 01-17

1

Glycyrrhiza glabra: A phytochemical and pharmacological review

Prof Dr Ali Esmail Al-Snafi Department of Pharmacology, College of Medicine, University of Thi qar, Iraq.

Corresponding Author: Prof Dr Ali Esmail Al-Snafi

Abstract: The phytochemical screening of the Glycyrrhiza glabra root revealed the presence of alkaloids,

glycosides, carbohydrates, starches, phenolic compounds, flavonoids, proteins, pectin, mucilage, saponins,

lipids, tannins, sterols and steroids. It showed memory enhancement, antidepressant, antimicrobial, anticancer,

antioxidant, protective, antiinflammatory, antiulcer, antidiabetic, hypolipidemic and many other

pharmacological effects. This review was designed to highlight the chemical constituents and pharmacological

effects of Glycyrrhiza glabra.

Keywords: Glycyrrhiza glabra, chemical constituents, pharmacology

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Date of Submission: 28-05-2018 Date of acceptance: 11-06-2018

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I. PLANT PROFILE:

Introduction:

In the last few decades there has been an exponential growth in the field of herbal medicine. It is

getting popularized in developing and developed countries owing to its natural origin and lesser side effects.

Plant derivates had been employed by population to prevent different kind of diseases for centuries. The

knowledge of plant properties was acquired by ancient civilization that passed down from generation to

generation until today. Plant showed wide range of pharmacological activities including antimicrobial,

antioxidant, anticancer, hypolipidemic, cardiovascular, central nervous, respiratory, immunological, anti-

inflammatory, analgesic antipyretic and many other pharmacological effects(1-33).

The phytochemical screening

of the Glycyrrhiza glabra root revealed the presence of alkaloids, glycosides, carbohydrates, starches, phenolic

compounds, flavonoids, proteins, pectin, mucilage, saponins, lipids, tannins, sterols and steroids. It showed

memory enhancement, antidepressant, antimicrobial, anticancer, antioxidant, protective, antiinflammatory,

antiulcer, antidiabetic, hypolipidemic and many other pharmacological effects. This review will highlight the

chemical constituents and pharmacological effects of Glycyrrhiza glabra.

Synonyms:

Glycyrrhiza brachycarpa Boiss., Glycyrrhiza glabra var. caduca X.Y. Li, Glycyrrhiza glabra var.

glabra, Glycyrrhiza glabra subsp. glandulifera (Waldst. & Kit.) Ponert, Glycyrrhiza glabra var.

glandulifera (Waldst. & Kit.) Regel & Herder, Glycyrrhiza glabra var. glandulifera (Waldst. & Kit.)

Boiss., Glycyrrhiza glabra var. glandulosa X.Y. Li, Glycyrrhiza glabra var. laxifoliolata X.Y. Li,

Glycyrrhiza glabra var. typica L., Glycyrrhiza glabra var. violacea (Boiss. & Noe) Boiss., Glycyrrhiza

glandulifera Waldst. & Kit., Glycyrrhiza hirsuta Pall., Glycyrrhiza pallida Boiss. & Noe, Glycyrrhiza

pallida Boiss and Glycyrrhiza violacea Boiss. & Noe(34)

.

Common names:

The genus name Glycyrrhiza was derived from the Greek glykys, for (sweet), and rhiza, for (root). The

species name glabra was derived from the Latin glaber, which means (smooth) or (bald) and refers to the smooth

husks. The plant common names were: Arabic: Sus, Irik Sus, rib el-sus; English: licorice, licorice-root,

liquorice; French: réglisse; German: Lakritze, Süßholz; Hindi: Mulhatti, Jethimadh, Mithilakdi; Italian:

liquirizia; Portuguese: alcaçuz, pau-doce; Spanish: alcazuz, licorice, orozuz, regaliz; Swedish: lakritsrot(35-36)

.

Distribution:

Glycyrrhiza glabra was native to Eurasia, northern Africa and western Asia. It was distributed in Africa

(Libya); Asia (Armenia, Azerbaijan, Georgia, Russian Federation, China, Kazakhstan,

Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan, Mongolia, Iran, Iraq, Afghanistan, Palestine,

Jordan, Lebanon, Syria, Turkey, India, Pakistan); and Europe (Moldova, Albania, Bulgaria, Russian

Federation-European part, Ukraine, Former Yugoslavia, Greece, Italy, Romania, France)(35)

.

Glycyrrhiza glabra: A phytochemical and pharmacological review

2

Traditional uses:

The dried rhizome and root have been used as expectorant and carminative by the Egyptian, Chinese,

Greek, Indian and Roman civilizations. Licorice was known in Chinese medicine as early as 2800 B.C. In Tibet,

it was considered a classical medicine. In the tomb of the Egyptian pharaoh Tutanchamon (1350 B.C.), the

healing power of licorice roots was described. The use of licorice preparations to alleviate throat and bronchial

infections was known for more than 2000 years(36)

.

Leaves were used externally for the treatment of wounds. Rhizome and root were used orally to treat

cystitis, kidney stones, lung ailment, diabetes, cough, stomachache, gastric ulcers, tuberculosis, Addison’s

disease, it was also used as mild laxative, contraceptive and to improve sexual function(37)

.

In addition, it was also used in sore throat, influenza, cold, bronchodilator, opthalmia, anti-syphilitic,

antidysenteric, gastric imbalance, indigestion, vomiting, diarrhea, swollen abscesses and as diuretic(38)

.

Furthermore, licorice was also used as a flavoring agent in the tobacco and candy industries and to

some extent in the pharmaceutical and beverage industries today(39)

.

Pats used medicinally: Leaves, root and rhizomes(37-38)

.

Physicochemical characteristics:

Physicochemical analysis of Glycyrrhiza glabra roots revealed that extractive values were (petroleum ether

4.67 ± 0.23%, chloroform 10.56 ± 1.53%, n-butanol, 6.54 ± 0.84% and methanol 13.89 ± 2.42%); ash values

were ( total ash 4.67 ± 0.35%, acid insoluble ash 0.56 ± 0.34% and water soluble ash 6.54 ± 0.22%); loss on

drying 5.87 ± 0.65%, moisture contents 0.56 ±0.054%, pH of the extract (1% solution) 5.04 ± 0.65, pH of the

extract (10% solution) 6.26 ± 0.54(40)

.

Chemical constituents:

The preliminary qualitative phytochemical screening of the ethanolic extract of Glycyrrhiza glabra

root revealed the presence of alkaloids, glycosides, carbohydrates, starches, phenolic compounds, flavonoids,

proteins, pectin, mucilage, saponins, lipids, tannins, sterols and steroids(40-41)

.

Liquorice root contained triterpenoid saponins (4–20%), mostly glycyrrhizin, a mixture of potassium

and calcium salts of 18β-glycyrrhizic acid ( which was the major bioactive compound in the underground parts,

which also called glycyrrhizic or glycyrrhizinic acid and a glycoside of glycyrrhetinic acid), it was 50 times

sweeter than sugar. Liquorice root also contained other triterpenes included liquiritic acid, glycyrretol,

glabrolide, isoglaborlide and liquorice acid. 18β-glycyrrhizic acid (3-O-(2-O-β-d- glucopyranuronosyl–α-d-

glucopyranurosyl)-3-β-hydroxy-11-oxo-18β,20β-olean-12-en-29-oic acid) was isolated from the roots of

Glycyrrhiza glabra(42-43)

.

The total phenolic contents of the ethanolic extract of Glycyrrhiza glabra root was 7.47 ± 0.05 mg/

gm of Gallic acid equivalent (GAE), while the total flavonoids contents was 2.25 ± 0.03 μg/gm quercetin

equivalents (QE)(40)

.

Flavonoids and chalcones isolated from Glycyrrhiza glabra included liquiritin, liquiritigenin,

hamnoliquiritin, neoliquiritin, chalcones isoliquiritin, isoliquiritigenin, neoisoliquiritin, licuraside, glabrolide,

licoflavonol, 5,8-dihydroxy-flavone-7-O-beta-D-glucuronide, glychionide A, and 5-hydroxy-8-methoxyl-

flavone-7-O-beta-D-glucuronide and glychionide B. Flavonoids were responsible for the yellow colour of

liquorice. Isoflavones: glabridin, galbrene, glabrone, shinpterocarpin, licoisoflavones A and B, formononetin,

glyzarin, kumatakenin, hispaglabridin A, hispaglabridin B, 4′-O-methylglabridin and 3′-hydroxy-4′-O-

methylglabridin, glabroisoflavanone A and B glabroiso-flavanone B were also isolated from Glycyrrhiza

glabra(44-46)

.

The essential oil of Glycyrrhiza glabra leaves was obtained by hydrodistillation and analyzed by GC

and GC-MS, showed that the main hydrocarbon and oxygen containing compounds were: isoniazid (13.36 %) ;

diethyltoluamide (6.56 %), benzoic acid (5.37 %), benzene (4.58 %), linalool (2.25 %), prasterone (5.63 %),

warfarin (1.43 %), iodoquinol (1.90 %), phenol, 4-(2-aminopropyl) (1.30 %), while 82 compounds were

identified in the root essential oil of Glycyrrhiza glabra, the main compounds identified from the root were

included hexanoic acid 31.57%, hexadecanoic acid 3.30%, hexanol 1.71% and octanoic acid 1.44%. The aroma

of this essential oil was considered to be a result of estragole (methyl chavicol), anethole, eugenol, indole

accompanied with γ-nonalactone and cumic alcohol(47-48)

.

Glycyrrhiza glabra samples taken from Egypt, Afghanistan, Syria, China, Bonn and Kiel were differ

in their types and quantities of volatile oils. However, the volatile oil identified in the Glycyrrhiza glabra

species root were: (E)-2-heptenal, 5-methyl- furfural, (2E, 1E) heptadienol, (E)-2-octen-1-al, o-guaiacol, 2-

phenylethanol, (Z)-pinene hydrate, lavandulol, terpinen-4-ol, (E)-linalool oxide, p-cymen-8-ol, α-terpineol,

methyl chavicol, (4E)-decenal, decanal, (2E, 4E)-nonadienal, cumin aldehyde, carvone, piperitone, (E)-

Glycyrrhiza glabra: A phytochemical and pharmacological review

3

cinnamaldehyde, (E)-anethole, (2E, 4Z)-decadienal, thymol, indole, carvacrol, (2E, 4Z)-decadienal, p-vinyl-

guaiacol, eugenol, γ-nonalactone, methyl eugenol, β-caryophyllene, β-dihydro-ionone, himachalene epoxide,

spathulenol, (1α, 10α)-Epoxy-amorph- 4-ene, β-caryophyllene oxide and humulene epoxide II(49)

.

The heavy metal residues in the ethanolic extract of Glycyrrhiza glabra root were: cadmium: 0.28 ±

0.03, lead: 0.48 ± 0.12, arsenic: 0.47 ± 0.05 and mercury: 0.33 ± 0.08 mg/ kg(40)

.

However, the percent of trace elements in the root powder of Glycyrrhiza glabra were: potassium:

0.66, calcium 1.87, sulphur 0.09, iron 0.14, aluminium 0.05, phosphorous 0.06, silicon 0.12, magnesium 0.17

and sodium 0.04%(50)

.

The chemical composition of raw, tea and infusion forms of licorice were: protein (%): 9.15 , 1.55 and

1.81; fat (%): 0.53, 0 and 0; moisture (%): 6.80 for raw; ash (%): 7.70, 0.02 and 0.15; fiber (%): 24.48, 0 and 0;

silica (%) : 3.56 , 0 and 0; for tea form, raw herb and infusion respectively. Carbohydrate: 47.11 for raw;

moisture: 6.80 for raw; calcium: 1720, 30 and 80 mg/100 ml; phosphorus: 78, 1 and 4 mg/100 ml;

sodium(ppm): 18580, 455.2 and 550; potassium (ppm): 7276, 178.4 and 215.1; zinc (ppm): 17.08, 0.118 and

undetectable; copper (ppm) 11.01, 0.076 and undetectable, for tea form, raw herb and infusion respectively.

The plant contained many amino acids included aspartic, glutamic, threonine, serine, proline, glycine, alanine,

valine, isoleucine, leucine, tyrosine, phenylalanine, histidine, tyrosine and lysine, it appeared that proline was

found to be the major free amino acid in the raw herb, licorice tea and infusion with concentrations of 1.02 %,

7.60 mg/100 ml and 6.80 mg/100 ml, respectively. Following in the order is aspartic acid, glutamic, valine and

the other amino acids. The major amino acids in the methanolic extract were aspartic (91.96 mg/100 ml)

followed by proline (77.14 mg/100 ml) and glutamic acid (27.05). HPLC analysis of the organic acids in the

licorice methanolic extract, tea and infusion forms revealed that the plant contained acetic, fumaric, butyric,

propanoic, malic, citic and tartaric acids. Tartaric acid was the predominant acid in the licorice methanolic

extract (3.5%), followed by butyric acid, malic acid, propanoic acid and citric acid. The tea form had butyric

acid (38.4 %) as a main acid followed by propanoic acid (0.33 %) and tartaric acid (0.22 %). The infusion form

had acetic acid (19.9 %) as a major organic acid(51)

.

Pharmacological effects:

Effect on memory and learning:

The effect of Glycyrrhiza glabra root extract (75, 150 and 300 mg/kg for 2 weeks) was evaluated on

learning and memory in three months old male rats. Elevated plus-maze and Morris water maze tests were

conducted to evaluate the learning and memory parameters as exteroceptive behavioral model and Diazepam

induced amnesia as interoceptive behavioral model. The aqueous extract of root of Glycyrrhiza glabra showed

improvement in learning and memory in a dose dependent manner. However, 150 mg/kg dose significantly

(P<0.01) enhanced learning and memory(52-53)

.

The beneficial effects of aqueous extract of Glycyrrhiza glabra root extract (75, 150, 225, and 300

mg/kg, for six successive weeks ) on learning and memory were studied in 1-month-old male Wistar albino rats

using the elevated plus maze, Hebb-William maze, and Morris water maze tests as exteroceptive behavioral

model and Diazepam-induced amnesia as interoceptive behavioral model. Results revealed that all the doses of

aqueous root extract of Glycyrrhiza glabra significantly enhanced the memory, the doses 150 and 225 mg/kg,

possessed significant (P < 0.01) enhancement in learning and memory. Furthermore, diazepam-induced

amnesia was reversed by the aqueous root extract of Glycyrrhiza glabra (150 and 225 mg/kg, po)(54)

.

The effects of aqueous extract of Glycyrrhiza glabra (75, 150 and 300 mg/kg po for 7 successive

days) on learning and memory was also evaluated in mice. Elevated plus-maze and passive avoidance paradigm

were employed to test learning and memory. The dose of 150 mg/kg of the aqueous extract of liquorice

significantly improved learning and memory of mice. This dose also significantly reversed the amnesia induced

by diazepam (1 mg/kg ip) and scopolamine (0.4 mg/kg ip)(55)

.

The dose of 150 mg/kg of the aqueous extract of Glycyrrhiza glabra for 7 successive days,

significantly improved learning and memory of mice and reversed the amnesia induced by diazepam (1 mg/kg

p), scopolamine (0.4 mg/kg ip), and ethanol (1 g/kg ip)(56)

.

The effects of Glycyrrhiza glabra on learning and memory were evaluated using object recognition

task (ORT) and elevated plus maze (EPM) models in mice. One dose level of aqueous liquorice extract

400mg/kg po, and two doses levels of glabridin rich extract 5mg/kg and 10mg/kg were administered orally in

separate groups of animals. Aqueous liquorice extract and glabridin 10mg/kg treatment significantly improved

learning and memory of mice by reversing the amnesia induced by scopolamine hydrobromide (2mg/kg, ip) and

diazepam (1mg/kg, ip)(57)

.

The effect of glabridin isolated from the roots of Glycyrrhiza glabra was investigated on cognitive

functions and cholinesterase activity in mice. Glabridin (1, 2 and 4 mg/kg, po) was administered daily for 3

successive days to mice. The higher doses (2 and 4 mg/kg po) of glabridin significantly antagonized the amnesia

induced by scopolamine (0.5 mg/kg ip) in both the elevated plus maze test and passive avoidance test.

Glycyrrhiza glabra: A phytochemical and pharmacological review

4

Glabridin (2 and 4 mg/kg po) also remarkably reduced the brain cholinesterase activity in mice compared to the

control group(58)

.

The effect of Glycyrrhiza glabra oral supplementation was evaluated on the mental intelligence and

memory function of the male students. Glycyrrhiza glabra tablets were formulated from the crude powder

prepared from roots and subjected to dose standardization process. 123 students were divided into two group,

treatment (1 tablet two times/ day) and placebo control (received starch powder) for the period of 60 days. Each

group was further subdivided into two, based on low and high intelligence percentage in order to avoid biasness.

Evaluation of improvement was judge by using NVIT (Non Verbal Intelligence Test) and memory test score

before the start and at the end of treatment period and scored them accordingly into poor, moderate, good and,

very good and expressed in percentage. The overall NVIT results indicated that oral consumption of Glycyrrhiza

glabra tablets twice a day improved the intelligence level among the student compared to placebo treatment.

Glycyrrhiza glabra treatment was found suitable without any side effects (59)

.

The deposition of senile plaque that is contributed mainly by amyloid-β (Aβ), whose production is

initiated by beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is one of the typical

hallmarks of Alzheimer’s disease. Inhibition of BACE1 is thereby is an attractive strategy for anti- Alzheimer’s

disease drug discovery. The natural product 2,2′,4′-trihydroxychalcone (TDC) from Glycyrrhiza

glabra functioned as a specific non-competitive inhibitor against BACE1 enzyme, and potently repressed β-

cleavage of APP and production of Aβ in human embryo kidney cells. The amelioration ability of this

compound against the in vivo memory impairment was further evaluated by APP-PS1 double transgenic mice

model. 9 mg/kg/day of TDC decreased Aβ production and Aβ plaque formation, and efficiently improve the

memory impairment based on Morris water maze test(60)

.

Antidepressant effect:

The effects of aqueous extract of Glycyrrhiza glabra on depression was investigated in mice using

forced swim test (FST) and tail suspension test (TST). The extract of Glycyrrhiza glabra (75, 150, and 300

mg/kg) was administered orally for 7 successive days in separate groups of male mice. The dose of 150 mg/kg

of the extract significantly reduced the immobility times of mice in both FST and TST, without any significant

effect on locomotor activity of mice. The efficacy of extract was found to be comparable to that of imipramine

(15 mg/kg ip) and fluoxetine (20 mg/kg ip). Liquorice extract reversed reserpine-induced extension of

immobility period of mice in FST and TST. Sulpiride (50 mg/kg ip, a selective D2 receptor antagonist) and

prazosin (62.5 μg/kg ip, an α1-adrenoceptor antagonist) significantly attenuated the extract-induced

antidepressant-like effect in TST. On the other hand, p-chlorophenylalanine (100 mg/kg ip, an inhibitor of

serotonin synthesis) did not reverse antidepressant-like effect of liquorice extract. It seemed that the

antidepressant-like effect of liquorice extract mediated by increase of brain norepinephrine and dopamine, but

not by increase of serotonin(61)

.

Antimicrobial effects:

The antibacterial effect of alcoholic extract obtained by percolation from roots of Glycyrrhiza glabra

was tested against Escherichia coli, Pseudomonas fluorescens, Enterococcus faecalis, Bacillus cereus, and

Staphylococcus aureus, the extract showed the strong antibacterial activity against all bacterial strains tested.

The maximum inhibition diameter was 15 mm against E. coli, E. faecalis, B.cereus, whereas P. fluorescens

showed the lowest sensitivity, with an inhibition zone of 9 mm(62)

.

The antimicrobial effect of the methanolic extract of Glycyrrhiza glabra was investigated against B.

megaterium, B. subtilis, Staphylococcus aureus, Sarcina lutea, Escherichia coli, Pseudomonas aeruginosa,

Salmonella paratyphi, S. typhi, Shigella boydii, S. dysenteriae, Vibrio mimicus and V. parahemolyticus.

Glycyrrhiza glabra methanolic extract showed potent antimicrobial activity against almost all the tested

organisms except Pseudomonas aeruginosa. It exhibited highest activity against Staphylococcus aureus with a

zone of inhibition of 22 mm(63)

.

The antimicrobial activity of methanolic extract and different fractions (n-butanol, ethyl acetate,

chloroform and n-hexane) of Glycyrrhiza glabra root was studied against four bacterial strains Escherichia coli,

Bacillus subtilis, Staphylococcus aureus and Pasturella multocida and three pathogenic fungi, Aspergillus niger,

Aspergillus flavus and Rhizopus solani using disc diffusion and minimum inhibitory concentration methods. As

general, plant extract and fractions were mildly potent antimicrobial agent. The results indicated that 100%

methanolic extract showed good activity against E. coli and B. subtilis, showing the highest inhibition zones (33

and 27.5 mm) and the lowest MIC values (9.28 and 30.2 mg/ml), respectively. Least activity was exhibited

against A. niger and R. solani with the smallest inhibition zones (16.5 and 16mm) and the highest MIC values

(150 and 152 mg/ml). 80% methanolic extract showed strong activity against B. subtilis and E. coli with

inhibition zones (30 and 28.5 mm) and the lowest MIC values (12.2 and 20.1 mg/ml), respectively. Least

activity was exihibited against S. aureus with inhibition zone (19 mm) and the highest MIC value (110 mg/ml),

Glycyrrhiza glabra: A phytochemical and pharmacological review

5

respectively. 80% methanolic fraction showed magnificent activity against A. niger as compared to standard

drug fluconazole(64)

.

The antibacterial effect of flavonoid extract of Glycyrrhiza glabra was tested against four pathogenic

bacterial strains: Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis and Staphylococcus aureus.

The antibacterial effect of the extract appeared concentration dependent. Flavonoids possessed an inhibitory

effect on both Staphylococcus aureus and Enterococcus faecalis but they showed less inhibitory effect against

Escherichia coli and Pseudomonas aeruginosa(65)

.

The antimicrobial activities of licorice tea and infusion (0.05, 0.1, 0.2, 0.4, 0.6 and 0.8%) were studied

against Bacillus subtilis, Staphylococcus aureus, Escherichiea coli, Salmonella and Saccharomyces cerevisiae.

The results revealed that these concentrations didn’t possess antibacterial activity(51)

.

The anti-bacterial activities of the methanol, ethyl acetate, acetone and chloroform extracts of

Glycyrrhiza glabra plant roots were tested against six bacterial species (Bacillus coagulans, Enterococcus

faecalis, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Salmonella typhimurium) by

the agar disc diffusion method. The results indicated that the extract of Glycyrrhiza glabra showed various

antibacterial activities (9-14mm/20μl inhibition zone) against the tested bacteria. The methanol, ethyl acetate,

acetone and chloroform extracts did not inhibit Enterococcus faecalis, Pseudomonas aeruginosa and

Staphylococcus aureus but showed an inhibitory effect against B. coagulans, E. coli and S. typhimurium(66)

.

The antibacterial potency of 100%, 75%, 50% and 25% of methanolic and acetonic extract of root of

Glycyrrhiza glabra was investigated against Salmonella typhi, Escherichia.coli, Vibrio cholerae,

Staphylococcus aureus, Bacillus cereus and Bacillus subtilis strains. The 100% (w/v) concentration of both

extracts showed maximum inhibition against Bacillus subtilis followed by Escherichia coli, Staphylococcus

aureus, Bacillus cereus, Salmonella typhi and Vibrio cholerae. Maximum activity in acetonic extract was

obtained against Bacillus cereus followed by Salmonella typhi, Escherichia coli, Vibrio cholerae and

Staphylococcus aureus and minimum in Bacillus subtilis. A reverse pattern of inhibition activity was found in

both extacts (methanolic and acetonic) against Bacillus subtilis. Maximum activity was found in methanolic

extract against Bacillus subtilis (18.6 mm) and in acetonic extract against Bacillus cereus (16.3mm)(67)

.

The antibacterial activity of Glycyrrhiza glabra was investigated against oral pathogens

[Streptococcus mutans (PTCC 1683), Streptococcus sanguis (PTCC 1449), Actinomyces viscosus (PTCC

1202), Enterococcus faecalis (ATCC 29212) as oral pathogens] and Staphylococcus aureus (ATCC 25923)

and Escherichia coli (ATCC 29922) as controls. Glycyrrhiza glabra extract possessed inhibitory activity

against the tested oral bacteria. No strain showed resistance to the extract. The inhibitory zone significantly

increased in a dose dependent manner(68)

.

The diameter of the inhibitory zone of the aqueous extract and methanolic extracts of the root of

Glycyrrhiza glabra, ranged between 10 - 22 mm against Staphylococcus aureus, Streptococcus agalactiae and

E. coli. The methanolic extract was more effective than aqueous extract against Staphylococcus aureus (20

mm), Streptococcus agalactiae (22 mm) and E. coli (17 mm) at the concentration of 8 mg/disc. The MIC values

of methanolic extract was 3.125 mg/ml for S. aureus, 1.56 mg/ml for St. agalactiae and 12.5 mg/ml for E. coli.

Whereas the aqueous extract showed higher MIC values, 6.25 mg/ml against S. aureus, 3.125 mg/ml for St.

agalactiae and the result was negative for E. coli(69)

.

Glycyrrhiza glabra root extracts (ether, chloroform, acetone) showed significant antibacterial activities

against two Gram-positive (Bacillus subtili and Stapphylococcus aureus) and two Gram-negative (Escherichia

coli and Pseudomonas aeruginosa) bacteria. Acetone extract showed the highest antibacterial activity with

diameter of inhibition of 32, 22, 22, 15 against Stapphylococcus aureus, Bacillus subtili, Pseudomonas

aeruginosa and Escherichia coli(70)

.

The antibacterial effect of the glycoside extracted from Glycyrrhiza glabra was investigated against

three bacterial strains, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. It showed

inhibitory effect on the Gram positive strain (Staphylococcus aureus ATCC23) and Gram negative strain

(Pseudomonas aeruginosa ATCC53), but it possessed no effect on Escherichia coli ATCC22 strain(71)

.

The antimicrobial effects of roots extracts of Glycyrrhiza glabra was investigated against

Staphylococcus aureus, Salmonella typhi, Staphylococcus sciuri, Escherichia coli, Aspergillus awamorii and

Rhizopus spp. The methanolic extract of Glycyrrhiza glabra showed maximum antibacterial activity against

Staphylococcus aureus at 500μg/ml (inhibition zone 13 mm) and maximum antifungal activity against

Rhizopus spp at 500μg/ml (inhibition zone 11 mm)(50)

.

The antimicrobial activities of ethanolic and aqueous extracts from licorice leaves were studied

compared to root extracts activities against Bacillus subtilis, Enterococcus faecalis, Klebsiella pneumoniae,

Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Candida albicans. The root and leave

extracts showed activity against Candida albicans and the tested Gram-positive bacteria in a dose dependent

manner. The ethanolic extract of the leaves was the most active extract against Gram-positive bacteria(72)

.

Glycyrrhiza glabra: A phytochemical and pharmacological review

6

Glabridin exhibited antimicrobial activity against both Gram-positive and Gram-negative bacteria, the highest

activity was recorded against Gram positive bacteria. Glabridin isolated from Glycyrrhiza glabra roots was

potentially active against both Mycobacterium tuberculosis H37Ra and H37Rv strains at 29.16 µg/ml

concentration(73)

.

The antimicrobial effect of root methanolic extracts of Glycyrrhiza glabra var. glandulifera was

investigated against nine bacterial and two yeast strains: six Gram-positive bacteria [Staphylococcus aureus

ATCC 6538, Enterococcus faecalis ATCC 51299, Micrococcus luteus, Bacillus cereus 7064, vancomycin-

resistant Enterococcus (VRE) and methycilline resistant Staphylococcus aureus (MRSA)]; three Gram negative

bacteria (Escherichia coli ATCC 11293, Pseudomonas aeruginos and Klebsiella pneumoniae) and two yeast

species (Candida krusei ATCC 6258 and Candida parapsilosis ATCC 22019)] using disc diffusion and

minimum inhibitory concentration methods. The results indicated that the plant root extracts were more

effective against Gram-positive bacteria than against Gram-negative ones. The plant methanolic extracts

inhibited the growth of B. cereus, E. faecalis, K. pneumonia, MRSA S. aureus, VRE, C. krusei and C.

parapsilosis. However, there was no activity against E. coli, K. pneumoniae and M. luteus. In addition, the

extracts had higher antimicrobial effect against Candida species than against bacteria(74)

.

The in vitro activity of glycyrrhizic acid, glycyrrhetinic acid and a novel lipophilic derivative of

glycyrrhetinic acid monoglucuronide acetylated GAMG was investigated against 29 Helicobacter pylori

strains. Glycyrrhetinic acid was the most potent compound (MIC 50 /90: 50/100 mg/l), inhibiting 79.3% of the

strains at MIC <50 mg/l(75)

.

The antifungal potential of the hydroalcoholic extract prepared from rhizomes and roots of

Glycyrrhiza glabra , was evaluated against 19 Candida strains, using the disc diffusion halo assay. The licorice

extract was effective against all the tested C. albicans, C. glabrata, C. parapsilosis and C. tropicalis strains. The

results for the inhibitory zones, at the tested concentration (50 mg/ml), after 24h, were 1.0 – 1.2 cm for C.

albicans and C. parapsilosis, 1.0 – 1.3 cm for C. tropicalis and 1.2 cm for C. glabrata(76)

.

Glycyrrhiza glabra extracts and glycyrrhizic acid inhibited the replication of several viruses included

Epstein-Barr virus, Herpes simplex virus, Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, Human

cytomegalovirus, Human immunodeficiency virus, Influenza virus, SARS coronavirus and Varicella zoster

virus(77-88)

.

Two coumarins of Glycyrrhiza glabra, glycocoumarin and licopyranocoumarin, inhibited giant cell

formation in HIV-infected cell cultures without any cytotoxicity. lichochalcone A also had anti-HIV activity(89-

90).

Glycyrrhizin was investigated as a therapy of human immuno-deficiency virus (HIV) in 42

hemophilia patients with HIV-1 infection. Patients showed improvement in their clinical symptoms (oral

candidiasis, lymph node swelling and rash), immunological functions and liver functions(91)

.

Many studies have demonstrated that glycyrrhizin was responsible for the antiviral activity of licorice.

The possible antiviral mechanisms of this compounds were (HCV): affected release step while infectious HCV

particles are infecting cells. Inhibited HCV full length viral particles and HCV core gene expression. (HSV):

reduced adhesion force and stress between CCEC and PMN. (CVB3): blocked the degradation of nuclear factor

κB inhibitor IκB. (DHV): activated T lymphocyte proliferation. (H5N1): weakened H5N1-induced production

of CXCL10, IL-6 and CCL5, and suppressed H5N1-induced apoptosis. (Influenza virus): reduced HMGB 1

binding to DNA, and inhibited influenza virus polymerase activity. ( CVA16 EV71): inactivated CVA16

directly, while the effect of anti-EV71 was associated with an events during the virus cell entry. (HSV1):

established a resistance state to HSV1 replication. (Rotavirus): reduced the levels of viral proteins VP2, VP6

and NSP2 at a step or steps subsequent to virus entry(92)

.

Anticancer effect:

The cytotoxic activity of the methanolic extract of Glycyrrhiza was tested using brine shrimp lethality

bioassay methods. The extract possessed potent cytotoxic activity with LC 50 value of 0.771μg/ml(63)

.

The antitumor activity of licorice methanolic extract (0, 12.5, 25, 50 and 100 μg/ml) was evaluated

against intestinal carcinoma cell line (Caco-2) and prostate carcinoma cell line (PC-3). Licorice methanolic

extract had a growth inhibitory action against Caco-2 and PC-3 with IC50 values of 40 and 40.6 μg/ml,

respectively(51)

.

Isoliquiritigenin isolated from the root of Glycyrrhiza glabra prevented the incidence of 1,2-

dimethylhydrazine-induced colon and lung tumors in mice when administered at a dose of 300 mg/kg(93)

.

The cytotoxic activity of different extracts of Glycyrrhiza glabra was tested on mice transformed cell

line. The results showed that hot alcoholic extract possessed the greatest cytotoxic effect on the cancer cells

(P <0.05) after 72 hourse exposure(94)

.

The effects of an ethanol extract of Glycyrrhiza glabra extract (50,100,150, and 200 μg/ml) was

investigated on the expression of HSP90, growth and apoptosis in the HT-29 colon cancer cell line. Results

Glycyrrhiza glabra: A phytochemical and pharmacological review

7

showed that Glycyrrhiza glabra inhibited proliferation of the HT-29 cell line at a concentration of 200 μg/ml,

this effect was confirmed by the highest rate of cell death as measured by trypan blue and MTT assays. RT-

PCR results showed down-regulation of HSP90 gene expression which confirmed the ability of Glycyrrhiza

glabra to induce apoptosis in HT-29 cells(95)

.

The antiangiogenic and antitumor activity of Glycyrrhiza glabra were investigated on VEGF and

MTA1 induced angiogenesis. The angio inhibitory activity of Glycyrrhiza glabra was confirmed by its

inhibition of angiogenesis, peritoneal and chorioallantoic membrane assay. Reduction in the levels of the

cytokine VEGF and microvessel density count in the peritoneum of mice treated with Glycyrrhiza glabra

indicated that the plant extract decreased VEGF production. It also inhibited the neovascularization in CAM

induced by VEGF and MTA1(96)

.

Antioxidant effect:

Chalcone derivative, a novel group of neolignan lipid esters, and seven known phenolic compounds

(formononetin, glabridin, hemileiocarpin, hispaglabridin B, isoliquiritigenin, 4‘-O-methylglabridin, and

paratocarpin B) isolated from the roots and stolons of Glycyrrhiza glabra were tested in an authentic

peroxynitrite anti-oxidant assay. Of these compounds, hispaglabridin B, isoliquiritigenin, and paratocarpin B

were found to be the most potent anti-oxidant agents(93)

.

The antioxidant effect of root methanolic extracts of Glycyrrhiza glabra var. glandulifera was

investigated using the DPPH (1,1-diphenyl-2-picrylhydrazyl) method. The extracts showed good antioxidant

activity, with a median inhibitory concentration (IC50) of 588 ± 0.86 to 2190 ± 1.73 mg/ml(74)

.

The free radical scavenging of the methanolic extract of Glycyrrhiza glabra was investigated using

DPPH. The extract showed moderate free radical scavenging activity with IC 50 value of 87.152 μg/ml(63)

.

The antioxidant activity of roots extracts of Glycyrrhiza glabra was investigated with DPPH

scavenging assay. The results revealed that methanolic extract of Glycyrrhiza glabra was potent antioxidant

with maximum scavenging effect of 67.22% at a concentration of 500μg/ml. The calculated IC50 for the

methanol extract of Glycyrrhiza glabra was 359.45μg/ml(50)

.

Effect on respiratory system:

The bronchorelaxant effect of Glycyrrhiza glabra was studied in a clinical trial (54 patients) in

comparison with Boswellia carterii (Olibanum) and prednisolone ( 18 patients each group) for 21 days.

Pulmonary function tests and serum electrolytes: calcium, magnesium, potassium and selenium were done

before and after the study. The results showed that the tested plants had significant elevation in the values of

forced expiratory volume in first second (FEV1%) as (72.45±5.83 vs 61.33±6.04 and 81.10±11.07 vs

62.30±7.22) for olibanum and licorice respectively. Also, elevation in the values of forced volume capacity

(FVC) with marked reduction in asthmatic attacks as (2.63±0.82 vs 0.72±0.16, 3.60±0.02 vs 1.08±0.08, and

2.25±0.16 vs 1.05± 0.15) for olibanum, licorice and prednisolone respectively, with better symptomatic

improvement in licorice group as compared to olibanum. Glycyrrhiza glabra was significantly elevated Mg:

from 0.66±0.17 to 1.02±0.10 , Se: from 28.19±3.72 to 51.70±8.63, Ca: from 1.90±0.06 2 to .30±0.08 and K:

from 3.60±0.03 to 4.10±0.12(97)

.

Glycyrrhiza decreased irritations in the throat and produced expectorant effects. It was assumed that

Glycyrrhiza was able to stimulate tracheal mucus secretions and produce demulcent and expectorant effects(98-

99).

Its powder and extract was useful for the treatment of sore throat, cough and bronchial catarrh. It also

possessed antitussive and expectorant(100)

.

Protective effects:

The hepatoprotective potential of aqueous (QGG) and ethanol extract of Glycyrrhiza glabra (EGG)

and their possible mechanism were studied in rats hepatotoxicity.For acute hepatopathy, rats were

intraperitoneally injected with CCl4 at a dose of 1.0 ml/kg as a 50% olive oil solution. The rats were orally given

the aqueous and ethanol extract of Glycyrrhiza glabra at doses of 250, 500 mg/kg after 6 h of CCl4 treatment.

At 24 h after CCl4 injection, samples of blood and liver were collected and then biochemical parameters and

histological studies were carried out. The results revealed that both extracts inhibited significantly the activities

of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) which elevated by CCl4 and increased

the activity of superoxide dismutase which decreased by CCl4(101)

.

Glycyrrhiza glabra: A phytochemical and pharmacological review

8

The hepatoprotective effect of aqueous extract (2gm/kg/day orally for 7 days) of Glycyrrhiza glabra

roots was investigated in rabbit models with acute liver injury induced by carbon tetrachloride at a dose of 1.25

ml/kg. Aqueous extract of Glycyrrhiza glabra had a significant effect in amiolerating liver functions as well as

restoring hepatic tissue in acute liver diseases(102)

.

The hepatoprotective and antioxidant potential of Glycyrrhiza glabra hydro-methanolic root extract

were investigated against carbon tetra chloride induced oxidative-stress mediated hepatotoxicity in liver tissue

of Swiss albino mice. The results suggested that, the crude extract of root of Glycyrrhiza glabra at the doses of

300 and 600mg/kg bw for 7 days possessed significant hepatoprotective potential against CCl4 induced

oxidative stress mediated hepatotoxicity (P<0.05) at dose dependent manner(103)

.

The protective effect of three medicinal plants, Nigella sativa, Glycyrrhiza glabra and Zingiber

officinale, and their combination was studied against doxorubicin (DOX) -induced apoptosis and death in H9c2

cells. The cells were incubated with different concentrations of each extract or their combination for 4 hr and

continued in the presence or absence of 5μM doxorubicin for 24 hr. Treatment with doxorubicin increased ROS

generation, enhanced malondialdehyde (MDA) formation, and induced apoptosis. Co-treatment of the cells with

each herb extract increased viability of cells dose-dependently with a maximum protection effect of about 30%,

and their potencies were Nigella sativa > Glycyrrhiza glabra > Zingiber officinale. The combination of the

threshold dose of each extract produced a similar effect, which was increased dose-dependently to a maximum

protection of 70%. These effects were correlated with the effects of the combination on ROS and MDA(104)

.

The efficacy of intravenous glycyrrhizin in decreasing alanine aminotransferase level in the early stage

of acute onset autoimmune hepatitis was studied clinically. Thirty-one patients defined as acute onset of

autoimmune hepatitis based on a uniform criteria, were enrolled in study. 17 patients were treated with

(100 ml/day) of intravenous glycyrrhizin at an early stage and 14 patients of severe disease were treated with

intravenous glycyrrhizin and corticosteroids. Treatment response, clinical and biochemical parameters were

evaluated. The alanine aminotransferase level could be controlled at an early stage using intravenous

glycyrrhizin with no significant difference compared with glycyrrhizin and corticosteroids. Recovery rate was

higher in the intravenous glycyrrhizin group than in the glycyrrhizin and corticosteroids group. The authors

concluded that sufficient doses of intravenous glycyrrhizin might prevent disease progression in patients with

acute onset autoimmune hepatitis(105)

.

The effect of Glycyrrhiza glabra on the metabolism of acetaminophen was examined in male rats.

The pretreatment with the methanol extract of Glycyrrhiza glabra roots (1 g/kg, po) for 6 days significantly

increased the cumulative biliary (156%) and urinary (132%) excretions of acetaminophen, glucuronide

conjugate within 120 min after the administration of acetaminophen (150 mg/kg, iv) without affecting thioether

and sulfate conjugates. In order to study the effect of Glycyrrhiza glabra on the glucuronidation in rat liver, the

enzymatic activity of p-nitrophenol UDP-glucuronosyltransferase (UGT), and intracellular concentrations of

hepatic UDP-glucuronic acid were examined upon the administration of Glycyrrhiza glabra (1 g/kg, po) or

glycyrrhizin (23 mg/kg, po), for 6 days. Glycyrrhiza glabra and glycyrrhizin caused increases in specific

activities of UGT1A by 111% and 96%, respectively. Concentration of UDP-glucuronic acid was increased

257% by Glycyrrhiza glabra and 484% by glycyrrhizin(106)

.

Anti-inflammatory effect:

The anti-inflammatory activity of hydro alcoholic extract of Glycyrrhiza glabra (HAEGG) root was

evaluated against carrageenan induced rat paw oedema at dose levels of 100, 200, and 300 mg/kg orally. The

hydro alcoholic extract of Glycyrrhiza glabra showed a maximum (46.86%) inhibitory action on carrageenan

induced paw oedema at the dose of 200 mg/kg and inhibited the leukocyte migration in a dose dependent

manner. The anti-inflammatory activity was comparable to indomethacin (10mg/kg)(66)

.

Several secondary metabolites isolated from rhizomes of Glycyrrhiza glabra were investigated for the

COX-2 inhibitory activity using Cayman COX (ovine) inhibitory screening assay. A few molecules showed

potent COX-2 inhibitory activity which may beneficial as anti-inflammatory agents(107)

Glycyrrhizin exhibited steroid-like anti-inflammatory activity, similar to hydrocortisone due to

inhibition of phospholipase A2 activity, glycyrrhizic acid inhibited cyclooxygenase activity and prostaglandin

formation (specifically prostaglandin E2), as well as indirectly inhibiting platelet aggregation(108-109)

.

Effect in gastric duodenal ulcers:

Carbenoxolone a glycyrrhizate analog was effective in clinical trials in the treatment of gastric and

duodenal ulcer at the medium dose of 100 mg three times a day. Liquorice can raise the concentration of

prostaglandins in the digestive system that promote mucus secretion from the stomach, it was also prolonged the

life span of surface cells in the stomach and has an anti-pepsin effects(110-114)

.

The anti- Helicobacter pylori activity of glycyrrhizic acid, glycyrrhetinic acid and a novel lipophilic

derivative of glycyrrhetinic acid monoglucuronide acetylated GAMG was tested against 29 Helicobacter pylori

Glycyrrhiza glabra: A phytochemical and pharmacological review

9

strains. Glycyrrhetinic acid was the most potent compound (MIC 50 /90, 50/100 mg/l), inhibiting 79.3% of the

strains at MIC <50 mg/l(75)

.

Forty patients receiving either 3.0 or 4.5 g deglycyrrhizinated licorice (DGL) daily for eight weeks,

were assessed for relief from epigastric pain, nausea, vomiting, x-ray of ulcer craters to determine changes in

size of ulcer, and frequency of relapse. All patients showed significant improvement after 5-7 days(115)

.

In more larger trial carried out on 874 patients with chronic duodenal ulcers. Patients were received

DGL, cimetidine, or antacids. No differences were recorded among groups in the rate of ulcer healing, but

patients in the DGL group showed less occurance of relapses(116)

.

Effect on smooth muscles:

The effect of the hydro-alcoholic extract of licorice rhizome on mechanical activity of isolated colon,

was studied in male rats. The mechanical activity of tissue in presence of extract and epinephrine was

significantly decreased (p≤0.05) compared to the control group. While the mechanical activity in the presence of

extract and propranolol was significantly increased (p≤0.05) compared to the control group. However, no

significant modification was observed in the mechanical activity of the tissue in the presence of phenylephrine

and extract compared to the control group. According to the result, it appeared that hydro-alcoholic extract of

licorice had modifying effect on colon motility via synergist effect with beta adrenergic receptors and

independent of the alpha adrenergic receptors(117-118)

.

Isoliquiritigenin isolated from an aqueous extract of licorice was a potent relaxant, it inhibited the

contraction induced by various types of stimulants, such as CCh, KCl, and BaCl2 with IC50 values of 4.96±1.97

microM, 4.03±1.34 microM and 3.70±0.58 microM(119-120)

.

The mechanisms of action of licorice rhizome extract on duodenal motility in vitro were investigated

in rats. Mechanical activity in response to extract 43μg/ml (most effective concentration based on

concentration/response experiments) in the presence of acetylcholine (10-5 M) as the muscarinic receptor

agonist, atropine (10-4 M) as the muscarinic receptor antagonist, epinephrine (10-6 M) as the β-adrenoceptor

agonist, propranolol as β receptor antagonist, or N-w- nitro- L arginine methyl ester (L-NAME) (10-4 M) as the

inhibitor of the NO synthase enzyme was measured. The results showed that the contraction force exerted on

the isolated duodenum pieces by acetylcholine was remarkably reduced in the presence of licorice rhizome

extract compared to that of the control group (P<0.05). However, this response in the presence of atropine,

propranolol and (L-NAME) was not changed significantly. According to the results of the study, alcoholic

extract of licorice rhizome decreases bowel motility. This inhibitory effect was independent of cholinergic, β-

adrenergic and nitrergic pathways(121)

.

Effect on diabetes:

The effects of long-term glycyrrhizin treatment (2.7, 4.1 g/kg diet) on diabetic symptoms were studied

using genetically non-insulin dependent diabetic model mice (KK-Ay). The elevation of blood glucose

concentration was almost entirely suppressed in mice fed the 0.41% glycyrrhizin diet 7 weeks after the

beginning of test feeding, although it was not suppressed in mice fed the control diet or the 0.27% glycyrrhizin

diet. Water intake in the control and 0.27% glycyrrhizin diet groups increased gradually, whereas, this was not

true in the 0.41% glycyrrhizin diet group. Glycyrrhizin treatment significantly lowered blood insulin level. It did

not affect the food intake or body weight. 0.41% glycyrrhizin diet in mice also improved their tolerance to oral

glucose loading 9 weeks after the beginning of test feeding(122)

.

The effect of glycyrrhizin was studied on streptozotocin (STZ)-induced diabetic changes and

associated oxidative stress, including haemoglobin-induced free iron-mediated oxidative reactions. Glycyrrhizin

treatment improved significantly the diabetogenic effects of STZ, it modulated blood glucose level, glucose

intolerant behaviour, decreased serum insulin level including pancreatic islet cell numbers, increased

glycohaemoglobin level and enhanced levels of cholesterol and triglyceride. The treatment significantly reduced

diabetes-induced abnormalities of pancreas and kidney tissues. Oxidative stress parameters, serum superoxide

dismutase, catalase, malondialdehyde and fructosamine in diabetic rats were reverted to respective normal

values after glycyrrhizin administration. Free iron in haemoglobin, iron-mediated free radical reactions and

carbonyl formation in haemoglobin were pronounced in diabetes, and were counteracted by glycyrrhizin. Effects

of glycyrrhizin and glibenclamide treatments appeared comparable(123)

.

Hypolipidemic effect:

Ethanolic extract and its ethyl acetate soluble, water soluble and hexane soluble fractions decreased

serum level of total cholesterol by 25.9, 38.0, 39.0 and 26.3%, respectively in high fructose diet induced

dsyslipidaemic in Syrian golden hamsters. Furthermore, they also increased the serum HDL-cholesterol level by

14.8, 34.3, 27.3 and 17.2%, and decreased triglyceride level by 31.3, 37.2, 41.2 and 28.9%, respectively. The

Glycyrrhiza glabra: A phytochemical and pharmacological review

10

reduction in LDL-cholesterol level by ethanolic extract, ethyl acetate soluble fraction and water soluble fraction

were 43.9, 31.0, 33.4 and 24.6%, respectively(124)

.

Effect on body weight:

In studying of body weight changes of rats pre-treated with licorice in infusion and tea forms, the results showed

that after 4-weeks, the mean values of body weight gains for control and pre-treated rats group with licorice

infusion and tea were 118.5, 132.6 and 121.7 gm (p ˂ 0.01) respectively. After 8-weeks, the group of male rats

drank licorice infusion were increased in weight than that of the control(51)

.

Effect on metabolic syndrome:

Therapeutic potential of Glycyrrhiza glabra root extract incorporated diet at 300 mg/kg/day was evaluated

in a rat model with high-fat diet-induced signs of metabolic syndrome. Glycyrrhiza glabra root extract

significantly reduced the weight of epididymal tissue (19.0%, p < 0.01) and basal serum glucose level (19.4%, p

< 0.05), decreased systolic blood pressure by 12.0% (p < 0.05), reduced serum IL6 and corticosterone levels

induced by HFD and reduced triacylglycerol accumulation in the liver(125)

.

Reproductive and hormonal effects:

The aphrodisiac activity of aqueous extract of Glycyrrhiza glabra roots and rhizomes was investigated

in rats. 150 mg/kg & 300 mg/kg/day were administered orally by gavage for 28 days. Mount latency,

intromission latency, mounting frequency, intromission frequency observed before and during the study at day

0, 7, 10, 14, 21, and 28. The extract reduced significantly mount latency and intromission latency. The extract

also increased significantly mounting frequency and intromission frequency(126)

.

Licorise showed mineralocorticoid properties due to the presence of glycyrrhizin and its metabolite

18β-glycyrrhetinic acid, which was an inhibitor of cortisol metabolism. It was suggest the mineralocorticoid

properties of liquorice, agonist of mineralocorticoid receptors and mild inhibitor of androgen synthesis, can

reduce the prevalence of side effects related to the diuretic activity of spironolactone in patients with PCOS

(Polycystic Ovarian Syndrome)(127-128)

.

18β-glycyrrhetinic acid, was a potent competitive inhibitor of 11β-HSD (11β-hydroxysteroid

dehydrogenase). Lowered 11β-HSD activity resulted in higher peripheral and intrarenal concentrations of

corticosterone in experimental animals and cortisol in humans, which interacted with mineralocorticoid

receptors and promote Na+

re-absorption. Acute pretreatment of adrenalectomized male rats with the the water-

soluble succinate derivative of 18β-glycyrrhetinic acid (carbenoxolone sodium) caused both cortisol and

corticosterone to display significant mineralocorticoid-like activity, particularly Na+

retention(129-130)

.

Glycyrrhiza glabra (25 mg alcoholic extract) showed high estrogenic activity reflected by uterine

response and vaginal opening. Based upon the mouse uterine weight method, three doses of 25 mg of the

alcoholic extract showed an estrogenic activity 1:4716980 of estradiol monobenzoate(131)

.

Six Glycyrrhiza phenols showed binding affinities for the bovine uterine estrogen receptor. The

affinity of a dihydrostilbene with two 3-methyl-2-butenyl (prenyl) groups, gancaonin R, was higher than those

of isoflavone phytoestrogens (genistein and daidzein) in dietary foods. The affinities of the other five phenols, a

flavanone (liquiritigenin), two prenylflavanones (isobavachin and sigmoidin B), a prenylated coumestan

(glycyrol), and a pyranoisoflav-3-ene (glabrene), were similar to that of the dietary isoflavone, genistein or

daidzein(132)

.

Effect on oral health, aphthous ulcer and lichen planus:

In a double‐blind, placebo‐controlled trial, 24 patients with recurrent aphthous ulcers were randomly

allocated to consume 2 g glycyrrhizin (carbenoxolone sodium) in 30 ml of warm water three times daily

following meals for four weeks. Oral licorice mouthwash significantly reduced the average number of ulcers per

day, pain scores, and the development of new ulcers compared with placebo. In another trial, 20 patients used

DGL mouthwash four times daily. 50‐75 percent clinical improvement was recorded in 15 patients after only

one day, with complete healing of canker sores after three days(133-134)

.

In an open clinical trial, 17 hepatitis C positive patients with oral lichen planus (an inflammatory disease

characterized by lymphocytic hyperkeratosis of the oral mucosa) were given either routine dental care or 40 ml

iv glycyrrhizin daily for one month. 66.7% of patients showed general clinical improvement, decreased redness,

fewer white papules, and less erosion of the mucosa(135)

.

Effect on the skin:

The extract of liquorice was reported to be an effective pigment lightening agent. Glabridin, in the

hydrophobic fraction of liquorice extract inhibited tyrosinase activity in cultured B16 murine melanoma cells.

Glabridin, licochalcone A and isoliquiritin were inhibited tyrosinase activity. In vitro tyrosinase enzyme

inhibition studies has showed that 21.2 μg/ml of methanolic extract of liquorice caused 50% tyrosinase enzyme

Glycyrrhiza glabra: A phytochemical and pharmacological review

11

inhibition. Due to good tyrosinase inhibition activity, liquorice extract can be used to formulate cosmetic

formulations with depigmenting activity. Ethanolic extract of Glycyrrhiza glabra was reported to show

improvement in the viscoelastic and hydration properties of the skin(136-138)

.

A double blind placebo controlled study was carried out on one hundred female volunteers suffering

from melasma (93 completed the study). Half of the females were used 2.5% of Glycyrrhiza glabra extract

cream and the other half were used placebo for 28 days. Comparison between the active treated cream and

placebo on week intervals, indicated a non significant improvement for the first week of the treatment course

(P=0.18). However, there was a significant difference in the improvement rate between the two treatment groups

for week 2 (P=0.009), week 3 (P=0.005) and week 4 (P=0.001)(139)

.

Liquorice showed hair growth stimulatory activity. Comparison between liquorice extract and

Minoxidil 2%, showed that, 2% concentration of liquorice hydro-alcoholic extract possessed better hair growth

stimulatory activity than 2% Minoxidil(140)

.

Immunological effect:

Neutrophils treated with alcoholic extract of Glycyrrhiza glabra showed increase in phagocytic

activity(141)

. The effect of Glycyrrhiza glabra root extract (0.1, 0.2 and 0.3 mg/l drinking water) was

investigated on the performance and some immunological parameters of broiler chickens. Glycyrrhiza glabra

root extract had no significant (P > .05) effect on immunological parameters including antibody titers against

Newcastle disease and Influenza viruses, heterophil and lymphocyte percentages and heterophil to lymphocyte

(H/L) ratio as well as liver and lymphoid organ (bursa of Fabricius, thymus and spleen) weights(142)

.

Side effects and contraindications:

LD50 values of Glycyrrhizin (crude extract 48-58%) in rats and mice: LD50 sc 4-4.4 g/kg, LD50 ip 1.42-1.70

g/kg and LD50 oral 14.2-18.0 g/kg(143)

.

At lower dosages or normal consumption levels, few adverse reactions were evident. Ocular effects and

hypersensitivity have been described. Hypertension and hypokalemia were recognized after excessive licorice

consumption. Large doses of glycyrrhizinic acid and glycyrrhetinic acid can lead to hypokalemia and serious

increases in blood pressure, a syndrome known as apparent mineralocorticoid excess. The majority of cases of

hypertension caused by liquorice were caused by eating too much liquorice candy(39,144-145)

.

Licorice with glycyrrhizin may cause serious side effects. Too much glycyrrhizin causes a condition called

pseudoaldosteronism, which can cause a person to become overly sensitive to a hormone in the adrenal cortex.

This condition can lead to headaches, fatigue, high blood pressure, and even heart attacks. It may also cause

water retention, which can lead to leg swelling and other problems. Although the dangerous effects mostly

happen with high doses of licorice or glycyrrhizin, smaller amounts of licorice may cause side effects. Some

people have muscle pain or numbness in the arms and legs(146)

.

Use during pregnancy should be avoided. Licorice exhibited estrogenic activity and possessed abortifacient

effects. There was no clinical evidence to support the use of licorice tea as a galactogogue(6)

. Glycyrrhizin

interacted with prednisolone, hydrocortisone and oral contraceptives(143)

.

Dose:

Licorice root has been used in daily doses from 1 to 15 g (2% glycyrrhizin) for ulcer and gastritis. Higher doses

given for extended periods of time may pose a risk of hyperkalemia. The acceptable daily intake for glycyrrhizin

was 0.2 mg/kg/day(39,144)

.

II. CONCLUSION: The review highlighted the chemical constituent, pharmacological and therapeutic effects of Glycyrrhiza

glabra as promising source of drugs because of its safety and effectiveness.

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